We have purified proteolytic enzymes from human skin, human epidermis, human lymphocytes, human fibroblasts, mouse skin and mouse epithelial cells in culture. One of these proteinases has been purified to homogeneity and it is a glycoprotein with a molecular weight of 30,000; enzymatic activity is inhibited by diisopropyl fluorophosphate. The enzyme induces dramatic polymorphonuclear leukocyte accumulation when it is injected into experimental animals. Phlogistic activity appears to be related to cleavage of complement components. Psoriatic plaques appear to contain increased amounts of the enzyme. The enzyme also appears to be cytotoxic to tissue culture cells. We will: extensively characterize this enzyme with regard to composition and function, develop an immunoassay for our enzyme, localize the enzyme in tissue and cells, investigate control mechanisms for enzymatic activity, determine the mechanism by which the enzyme induces polymorphonuclear leukocyte accumulation and evaluate its role in keratinization. We will also study a number of disease with special emphasis on psoriasis to determine the pathophysiological role of proteinases and hydrolases. We will evaluate the therapeutic utility of proteinase inhibitors in selected clinical diseases.